【摘要】 目的 探讨维甲酸相关孤核受体(ROR)α/β-catenin/转化生长因子(TGF)-β1/Rac1轴在二烯丙基二硫(DADS)与SR1078作用下对人胃癌细胞的迁移侵袭与上皮间质转化(EMT)的影响。方法 实验分为MGC803组、DADS组与SR1078组。噻唑蓝(MTT)、划痕实验和迁移侵袭实验分别检测细胞增殖、迁移与侵袭。Western印迹与免疫荧光检测RORα/β-catenin/TGF-β1/Rac1轴相关分子表达，相差显微镜观察形态改变。结果 SR1078与DADS作用24、48、72、96 h后，增殖活性均较MGC803组明显降低(P<0.01),而SR1078组与DADS组比较无明显差异(P>0.05)。24 h后划痕距离，SR1078组和DADS组较MGC803组明显缩短(P<0.05),而SR1078组与DADS组无显著差异(P>0.05)。DADS组与S1078组迁移及侵袭细胞较MGC803组显著减少(P<0.05),而SR1078组与DADS组无显著差异(P>0.05)。与MGC803组比较，DADS组和SR1078组RORα蛋白明显上调(P<0.05)。SR1078组与DADS组核内β-catenin蛋白表达较MGC803组显著降低(P<0.05),两者作用效果相当。与MGC803组比较，DADS组与SR1078组细胞异形性明显降低，TGF-β1、Rac1、Vimentin表达明显下调，而E-cadherin明显上调(P<0.000 1)。结论 DADS与SR1078作用于人胃癌MGC803细胞后，可抑制其增殖、迁移、侵袭与EMT的能力，可能是通过RORα/β-catenin/TGF-β1/Rac1轴起作用的，因此，提示DADS与SR1078作用相似，可能是一种新型RORα激动剂。更多还原

【Abstract】 Objective To investigate the effects of diallyl disulfide(DADS) and SR1078 on the migration, invasion and epithelial-mesenchymal transformation(EMT) of human gastric cancer cells via the retinoic acid-associated solitary nucleus receptor(ROR)α/β-catenin/transforming growth factor(TGF)-β1/Rac1 axis.Methods The experiment was divided into MGC803 group, DADS group and SR1078 group. Cell proliferation, migration and invasion were detected by thiazolyl blue(MTT), scratch experiment, migration and invasion experiments, respectively. Western blot and immunofluorescence were used to detect the expressions of RORα/β-catenin/TGF-β1/Rac1 axis-related molecules, and the morphological changes were observed by phase contrast microscopy. Results The proliferative activity of SR1078 and DADS after 24, 48, 72 and 96 h treatment were decreased compared with MGC803 group(P<0.05), there was no significant difference between SR1078 and DADS groups(P>0.05). The scratch distance of SR1078 group and DADS group was significantly shorter than that in MGC803 group after 24 h(P<0.05),there was no significant difference between SR1078 group and DADS group(P>0.05). Compared to the MGC803 group, the number of migrating and invading cells in the DADS and SR1078 groups was significantly reduced(P<0.05), there was no significant difference between the SR1078 and DADS groups(P>0.05). Compared with the MGC803 group, the RORα protein was significantly up-regulated in the DADS and SR1078 groups(P<0.05). The expression of Nucleus-β-catenin protein of SR1078 and DADS groups was significantly decreased compared with MGC803 group(P<0.05), and the effect of the two groups was similar. Compared with MGC803 group, cell atypia was significantly decreased, TGF-β1, Rac1 and Vimentin expressions were significantly decreased, while E-cadherin expression was significantly increased in DADS and SR1078 groups(P<0.000 1). Conclusions DADS and SR1078 could inhibit the proliferation, migration, invasion and EMT of human gastric cancer MGC803 cells, possibly through the RORα/β-catenin/TGF-β1/Rac1 axis, suggesting that DADS and SR1078 have similar effects, which may be a novel RORα agonist.更多还原